Abstract
Histone lysine acetylation orchestrates transcriptional activity essential for diverse cellular events across organisms, but it remains poorly understood how an acetylated lysine affects cellular functions in filamentous fungal pathogens. Here, we show the functions of a histone acetyltransferase that is phylogenetically close to Mst2 in fission yeast and specifically acetylates histone H3K14 in Beauveria bassiana, a fungal insect pathogen widely applied in arthropod pest management. Deletion of mst2 in B. bassiana resulted in moderate growth defects on rich and minimal media, delayed conidiation, and drastic reduction (75%) in conidiation capacity under normal culture conditions. The Δmst2 conidia suffered slower germination, decreased hydrophobicity, attenuated virulence, and reduced thermotolerance and UV-B resistance. The Δmst2 mutant also displayed increased sensitivities to DNA damaging, oxidative, cell wall perturbing, and osmotic stresses during conidial germination and colony growth at optimal 25 °C. Intriguingly, the phenotypic changes were accompanied with transcriptional repression of related gene sets, which are required for asexual development and conidial hydrophobicity or cascaded for CWI and HOG pathways, and encode the families of superoxide dismutases (SOD), catalases, heat-shock proteins, and trehalose or mannitol-metabolizing enzymes. Consequently, total SOD and catalase activities, trehalose and mannitol contents, and hydrophobicity were remarkably lowered in the hyphal cells or conidia of Δmst2. All of these changes were well restored by targeted mst2 complementation. Our results indicate that Mst2 enables to mediate global gene transcription and/or post-translation through H3K14 acetylation and plays an essential role in sustaining the biological control potential of B. bassiana against arthropod pests.





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References
Carlson S, Glass KC (2014) The MOZ histone acetyltransferase in epigenetic signaling and disease. J Cell Physiol 229:1571–1574
Carrozza MJ, Utley RT, Workman JL, Cote J (2003) The diverse functions of histone acetyltransferase complexes. Trends Genet 19:321–329
Cavero S, Herruzo E, Ontoso D, San-Segundo PA (2016) Impact of histone H4K16 acetylation on the meiotic recombination checkpoint in Saccharomyces cerevisiae. Microbial Cell 3:606–620
Chen Y, Zhu J, Ying SH, Feng MG (2014) Three mitogen-activated protein kinases required for cell wall integrity contribute greatly to biocontrol potential of a fungal entomopathogen. PLoS One 9:e87948
Chu ZJ, Sun HH, Zhu XG, Ying SH, Feng MG (2017) Discovery of a new intravacuolar protein required for the autophagy, development and virulence of Beauveria bassiana. Environ Microbiol 19:2806–2818
de Faria MR, Wraight SP (2007) Mycoinsecticides and mycoacaricides: a comprehensive list with worldwide coverage and international classification of formulation types. Biol Control 43:237–256
Donatti AC, Furlaneto-Maia L, Fungaro MHP, Furlaneto MC (2008) Production and regulation of cuticle-degrading proteases from Beauveria bassiana in the presence of Rhammatocerus schistocercoides cuticle. Curr Microbiol 56:256–260
Elbein AD, Pan YT, Pastuszak I, Carroll D (2003) New insights on trehalose: a multifunctional molecule. Glycobiology 13:17R–27R
Etxebeste O, Garzia A, Espeso EA, Ugalde U (2010) Aspergillus nidulans asexual development: making the most of cellular modules. Trends Microbiol 18:569–576
Gao BX, Kong QF, Zhang YN, Yun CW, Dent SYR, Song JX, Zhang DD, Wang YM, Li XM, Fang DY (2017) The histone acetyltransferase Gcn5 positively regulates T cell activation. J Immunol 198:3927–3938
Gillespie JP, Bateman R, Charnley AK (1998) Role of cuticle-degrading proteases in the virulence of Metarhizium spp. for the desert locust, Schistocerca gregaria. J Invertebr Pathol 71:128–137
Gómez EB, Espinosa JM, Forsburg SL (2005) Schizosaccharomyces pombe mst2 + encodes a MYST family histone acetyltransferase that negatively regulates telomere silencing. Mol Cell Biol 25:8887–8903
Grant PA (2001) A tale of histone modifications. Genome Biol (2):reviews0003.1–reviews0003.6
Holder DJ, Kirkland BH, Lewis MW, Keyhani NO (2007) Surface characteristics of the entomopathogenic fungus Beauveria (Cordyceps) bassiana. Microbiol-SGM 153:3448–3457
Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080
Jeon J, Kwon S, Lee YH (2014) Histone acetylation in fungal pathogens of plants. Plant Pathol J 30:1–9
Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705
Lee KK, Workman JL (2007) Histone acetyltransferase complexes: one size doesn’t fit all. Nat Rev Mol Cell Biol 8:284–295
Li F, Shi HQ, Ying SH, Feng MG (2015a) WetA and VosA are distinct regulators of conidiation capacity, conidial quality, and biological control potential of a fungal insect pathogen. Appl Microbiol Biotechnol 99:10,069–10,081
Li F, Shi HQ, Ying SH, Feng MG (2015b) Distinct contributions of one Fe- and two Cu/Zn-cofactored superoxide dismutases to antioxidation, UV tolerance and virulence of Beauveria bassiana. Fungal Genet Biol 81:160–171
Lin YY, Lu JY, Zhang JM, Walter W, Dang WW, Wan J, Tao SC, Qian J, Zhao YM, Boeke JD, Berger SL, Zhu H (2009) Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. Cell 136:1073–1084
Liu Q, Ying SH, Feng MG, Jiang XH (2009) Physiological implication of intracellular trehalose and mannitol changes in response of entomopathogenic fungus Beauveria bassiana to thermal stress. Antonie van Leeuwenhoek 95:65–75
Liu Q, Ying SH, Feng MG (2011) Characterization of Beauveria bassiana neutral trehalase (BbNTH1) and recognition of crucial stress-responsive elements to control its expression in response to multiple stresses. Microbiol Res 166:282–293
Liu Q, Ying SH, Li JG, Tian CG, Feng MG (2013) Insight into the transcriptional regulation of Msn2 required for conidiation, multi-stress responses and virulence of two entomopathogenic fungi. Fungal Genet Biol 54:42–51
Liu J, Wang ZK, Sun HH, Ying SH, Feng MG (2017) Characterization of the Hog1 MAPK pathway in the entomopathogenic fungus Beauveria bassiana. Environ Microbiol 19:1808–1821
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods 25:402–408
Maltby VE, Martin BJE, Brind’Amour J, Chruscicki AT, McBurney KL, Schulze JM, Johnson IJ, Hills M, Hentrich T, Kobor MS, Lorincz MC, Howe LJ (2014) Histone H3K4 demethylation is negatively regulated by histone H3 acetylation in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 109:18,505–18,510
Marmorstein R, Trievel RC (2009) Histone modifying enzymes: structures, mechanisms, and specificities. BBA-Gene Regul Mech 1789:58–68
Nugent RL, Johnsson A, Fleharty B, Gogol M, Xue-Franzén Y, Seidel C, Wright APH, Forsburg SL (2010) Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation. BMC Genomics 11:59–75
Park HS, Yu JH (2012) Genetic control of asexual sporulation in filamentous fungi. Curr Opin Microbiol 15:669–677
Petty EL, Lafon A, Tomlinson SL, Mendelsohn BA, Pillus L (2016) Promotion of cell viability and histone gene expression by the acetyltransferase Gcn5 and the protein phosphatase PP2A in Saccharomyces cerevisiae. Genetics 203:1693–1727
Rodriguez ME, Orozco H, Cantoral JM, Matallana E, Aranda A (2014) Acetyltransferase SAS2 and sirtuin SIR2, respectively, control flocculation and biofilm formation in wine yeast. FEMS Yeast Res 14:845–857
Ruijter GJG, Bax M, Patel H, Flitter SJ, van de Vondervoort PJI, de Vries RP, vanKuyk PA, Visser J (2003) Mannitol is required for stress tolerance in Aspergillus niger conidiospores. Eukaryot Cell 2:690–698
Sapountzi V, Côté J (2011) MYST-family histone acetyltransferases: beyond chromatin. Cell Mol Life Sci 68:1147–1156
Shen Y, Wei W, Zhou DX (2015) Histone acetylation enzymes coordinate metabolism and gene expression. Trends Plant Sci 20:614–621
Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45
Thomas T, Voss AK (2007) The diverse biological roles of MYST histone acetyltransferase family proteins. Cell Cycle 6:696–704
van Leeuwen F, Gottschling DE (2002) Genome-wide histone modifications: gaining specificity by preventing promiscuity. Curr Opin Cell Biol 14:756–762
Vetting MW, de Carvalho LPS, Yu M, Hegde SS, Magnet S, Roderick SL, Blanchard JS (2005) Structure and functions of the GNAT superfamily of acetyltransferases. Arch Biochem Biophys 433:212–226
Vicente-Munoz S, Romero P, Magraner-Pardo L, Martinez-Jimenez CP, Tordera V, Pamblanco M (2014) Comprehensive analysis of interacting proteins and genome-wide location studies of the Sas3-dependent NuA3 histone acetyltransferase complex. FEBS Open Bio 4:996–1006
Wang CS, Feng MG (2014) Advances in fundamental and applied studies in China of fungal biocontrol agents for use against arthropod pests. Biol Control 68:129–135
Wang J, Ying SH, Hu Y, Feng MG (2016) Mas5, a homolog of bacterial DnaJ, is indispensable for the host infection and environmental adaptation of a filamentous fungal insect pathogen. Environ Microbiol 18:1037–1047
Wang JJ, Qiu L, Cai Q, Ying SH, Feng MG (2014) Three α-1,2-mannosyltransferases contribute differentially to conidiation, cell wall integrity, multistress tolerance and virulence of Beauveria bassiana. Fungal Genet Biol 70:1–10
Wang JJ, Cai Q, Qiu L, Ying SH, Feng MG (2017) Additive roles of two TPS genes in trehalose synthesis, conidiation, multiple stress responses and host infection of a fungal insect pathogen. Appl Microbiol Biotechnol 101:3637–3651
Wang X, Chang P, Ding J, Chen J (2013a) Distinct and redundant roles of the two MYST histone acetyltransferases Esa1 and Sas2 in cell growth and morphogenesis of Candida albicans. Eukaryot Cell 12:438–449
Wang Y, Kallgren SP, Reddy BD, Kuntz K, López-Maury L, Thompson J, Watt S, Ma C, Hou H, Shi Y (2012a) Histone H3 lysine 14 acetylation is required for activation of a DNA damage checkpoint in fission yeast. J Biol Chem 287:4386–4393
Wang ZL, Lu JD, Feng MG (2012b) Primary roles of two dehydrogenases in the mannitol metabolism and multi-stress tolerance of entomopathogenic fungus Beauveria bassiana. Environ Microbiol 14:2139–2150
Wang ZL, Zhang LB, Ying SH, Feng MG (2013b) Catalases play differentiated roles in the adaptation of a fungal entomopathogen to environmental stresses. Environ Microbiol 15:409–418
Xiao GH, Ying SH, Zheng P, Wang ZL, Zhang SW, Xie XQ, Shang YF, Zheng HJ, Zhou Y, St Leger RJ, Zhao GP, Wang CS, Feng MG (2012) Genomic perspectives on the evolution of fungal entomopathogenicity in Beauveria bassiana. Sci Rep 2:483
Xie XQ, Li F, Ying SH, Feng MG (2012) Additive contributions of two manganese-cored superoxide dismutases (MnSODs) to antioxidation, UV tolerance and virulence of Beauveria bassiana. PLoS One 7:e30298
Zhang Q, Chen LF, Yu X, Liu H, Akhberdi O, Pan J, Zhu XD (2016) A B-type histone acetyltransferase Hat1 regulates secondary metabolism, conidiation, and cell wall integrity in the taxol-producing fungus Pestalotiopsis microspora. J Basic Microbiol 56:1380–1391
Zhang SZ, Xia YX, Kim B, Keyhani NO (2011) Two hydrophobins are involved in fungal spore coat rodlet layer assembly and each play distinct roles in surface interactions, development and pathogenesis in the entomopathogenic fungus, Beauveria bassiana. Mol Microbiol 80:811–826
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This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 31600063 and 31772218).
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Wang, JJ., Cai, Q., Qiu, L. et al. The histone acetyltransferase Mst2 sustains the biological control potential of a fungal insect pathogen through transcriptional regulation. Appl Microbiol Biotechnol 102, 1343–1355 (2018). https://doi.org/10.1007/s00253-017-8703-9
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DOI: https://doi.org/10.1007/s00253-017-8703-9


